Table of Contents

Focus of Research for Clinicians

A systematic review of 63 clinical studies published from 1966 to October 2011 examined the comparative effectiveness, benefits, and adverse effects of progestogens used to prevent preterm birth in several categories of at-risk women. The full report listing all studies and the results of the analysis is available at www.effectivehealthcare.ahrq.gov/pretermbirth.cfm. This summary, based on the full report of research evidence, is provided to inform discussions of options with patients and to assist in decisionmaking along with consideration of a patient’s values and preferences. However, reviews of evidence should not be construed to represent clinical recommendations or guidelines.

Background Information

Preterm births, which occur before completion of 37 weeks of pregnancy, are associated with more than 85 percent of perinatal morbidity and mortality, both maternal and infant. In the United States, 12.5 percent of live births each year are preterm, but efforts to reduce the rate have been unsuccessful.

The current clinical focus is on early intervention based on risks. In the United States, about 133,000 pregnant women per year have a history of spontaneous preterm birth and are candidates for intervention. A natural role of progesterone is to help maintain pregnancy. As evidence accrues from controlled trials, the use of progestogens (natural and synthetic progestin forms of progesterone) for women with prior preterm birth is increasingly regarded as beneficial.

Still, progestogen use for these women is limited by lack of synthesized evidence about effectiveness, optimal formulations, administration routes, doses and timing of drug delivery, modifiers of treatment effect, and a need for more data on short- and long-term risks. Also unresolved is whether other at-risk groups can benefit from progestogens.

Conclusions

Progestogens reduce the risk of preterm birth for women with prior spontaneous preterm births and current singleton pregnancies. Women with a short cervix may also benefit, but the evidence is limited. For women with multiple gestations, there is no benefit. For all other indications, the evidence is insufficient to guide care. The incidence of rare adverse events and the effects of modifiers are unknown, and direct comparisons of progestogen formulations, doses, timing, and durations of use have not been made. The evidence is insufficient to know whether progestogen use prevents morbidity or promotes normal childhood development.

Clinical Bottom Line

Benefits

By Indication (Risk Group)

For women with current singleton pregnancies and a history of spontaneous preterm birth who are treated with progestogens:

By Formulation/Route of Administration

When assessed by routes of administration alone (injected, oral, and vaginal), all formulations reduce the risk of preterm birth, but none reduce neonatal mortality rates. (Strength of evidence not rated)

Without head-to-head trials, the evidence is insufficient to determine if formulation and administration route are associated with different maternal or fetal outcomes or adverse effects.

Adverse Effects

Safety of Progestogens

Study withdrawal rates (a measure of tolerability) were similar for treated and control groups.

What To Discuss With Your Patients

Progestogens reduce the risk of preterm birth for women who previously had a spontaneous preterm birth and who currently have a singleton pregnancy. Women with a short cervix may also benefit. Progestogens do not prevent preterm birth for twin or triplet gestations.

There is little evidence about using progestogens for women with preterm labor or other risk factors for preterm birth.

The evidence about differences between the oral, injection, or vaginal methods for treatment is limited.

It is not known if progestogens will provide short- or long-term benefits to the infant or pregnant woman, other than delaying birth, and there is little evidence about short- and long-term adverse effects.

This summary was prepared by the John M. Eisenberg Center for Clinical Decisions and Communications Science at Baylor College of Medicine, Houston, TX. It was written by Diane Markesich, Ph.D., Thomas Workman, Ph.D., Kjersti Aagaard-Tillery, M.D., and Michael Fordis, M.D.